Bipolar Androgen Therapy in Metastatic Castrate Resistant Prostate Cancer With Homologous Recombination Deficiency (HiTeCH)
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|ClinicalTrials.gov Identifier: NCT03522064|
Recruitment Status : Recruiting
First Posted : May 11, 2018
Last Update Posted : September 18, 2019
|Condition or disease||Intervention/treatment||Phase|
|Castration-resistant Prostate Cancer Homologous Recombination Deficiency||Drug: Testosterone Enanthate||Phase 2|
Androgen deprivation therapy (ADT) remains the mainstay of prostate cancer treatment. Though an effective therapy initially, the side effects of ADT are numerous and treatment resistance is inevitable. Castrate-refractory prostate cancer (CRPC) progresses via adaptive mechanisms that allow ongoing androgen receptor (AR) signalling despite castrate levels of androgens.
The concept of cycling between supra- and sub physiological levels of testosterone has been tested recently in studies of "bipolar androgen therapy" (BAT) in which patients are given high dose testosterone in combination with androgen deprivation therapy (ADT) via an LHRH agonist/antagonist. Studies of BAT using IM testosterone have been promising both in terms of PSA responses and quality of life improvements. Additionally, these early phase studies suggest the potential for re-sensitisation to novel anti-androgen therapies.
Though responses have been positive in these early studies a proportion of men fail to respond and data to guide patient selection is lacking. There are data to suggest that patients with DNA repair deficits may be particularly responsive to BAT. Whether these changes serve as predictors of response is unknown as the effect of BAT on the tumour, its microenvironment and peripheral circulating tumour DNA has not been studied in detail. Information on treatment effects may be key to appropriate patient selection for this treatment.
The aim of this study is to assess homologous repair deficiency as a predictive biomarker of response to bipolar androgen therapy in men with metastatic castrate-refractory prostate cancer and to study the effects of this treatment on ctDNA and intra-tumoural gene expression.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||High Dose Testosterone in Men With Advanced Prostate Cancer and Homologous Recombination Deficiency|
|Actual Study Start Date :||July 30, 2018|
|Estimated Primary Completion Date :||July 30, 2021|
|Estimated Study Completion Date :||July 30, 2021|
Experimental: High dose testosterone
500mg IM enanthate every 4 weeks in combination with ongoing LHRH agent (unless post-orchidectomy).
Drug: Testosterone Enanthate
Testosterone Enanthate is the oil-soluble ester of the androgenic hormone testosterone. Testosterone Enanthate is a clear to pale yellow solution for intramuscular injection. Each pre-filled syringe contains 250mg testosterone enanthate/1mL.
Other Name: Primoteston Depot
- PSA Response Rate [ Time Frame: 1 year ]>/= 50% fall from baseline PSA
- Time to PSA progression [ Time Frame: 1 year ]Time to increase in PSA >/=25% from baseline or nadir confirmed on subsequent test >1 week later
- Quality of Life [ Time Frame: 1 year ]FACT-P
- Radiological Response Rate [ Time Frame: 1 year ]RECIST or PCWG3 Criteria
- Safety and Tolerability (Frequency of adverse events as assessed by NCI CTCAE v4.0) [ Time Frame: 1 year ]Frequency of adverse events as assessed by NCI CTCAE v4.0
- Changes in ctDNA expression from baseline [ Time Frame: 1 year ]Exploratory
- Change in serum testosterone and oestradiol levels [ Time Frame: 1 year ]Change in serum levels from baseline to Days 14 and 28 of cycle 1
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03522064
|Contact: Robert Kent||+61293555611||SVHS.CancerResearch@svha.org.au|
|Australia, New South Wales|
|Kinghorn Cancer Centre, St. Vincent's Hospital||Recruiting|
|Sydney, New South Wales, Australia, 2010|
|Contact: Robert Kent 0293555611 SVHS.CancerResearch@svha.org.au|
|Principal Investigator:||Anthony M Joshua, MBBS, PhD, FRACP||St. Vincent's Hospital-Manhattan|